Inclusive multisensory science and immunology books for blind, low-vision and diverse-needs audiences.

This paper presents interdisciplinary research exploring the development of inclusive multisensory science books, communicating immunology data for blind, low-vision and diverse-needs audiences. The research adopted an inductive theory-building approach, practice-based art methods and music and design methods, leveraging the lived experience of a legally blind artist. The research also involved designers and scientists in a cocreation process, producing books that incorporate tactile artworks, Braille-inspired protein models, image sonification and interaction. Two multisensory book titles, "The Heroes Within You: A Multisensory Exploration of Infection and Immunity" and "My Goodness: A Multisensory Exploration of Nutrition and Immunity", were developed for the Monash Sensory Science 2023 Exhibition Day. The books offer an innovative way to make science and art more accessible and engaging, addressing the limitations of traditional museum methods. Feedback from audiences has been positive, emphasizing the fascination, sensory engagement and ease of understanding. This paper highlights the potential for an interdisciplinary and inclusive approach to science and art, demonstrating the value of multisensory books as tools for science communication. The findings highlight the positive reception of this novel approach and suggest its potential for broader applications, promoting inclusivity and accessibility.

Multifunctional Biocatalysts for Organic Synthesis.

Biocatalysis is becoming an indispensable tool in organic synthesis due to high enzymatic catalytic efficiency as well as exquisite chemo- and stereoselectivity. Some biocatalysts display great promiscuity including a broad substrate scope as well as the ability to catalyze more than one type of transformation. These promiscuous activities have been applied individually to efficiently access numerous valuable target molecules. However, systems in which enzymes possessing multiple different catalytic activities are applied in the synthesis are less well developed. Such multifunctional biocatalysts (MFBs) would simplify chemical synthesis by reducing the number of operational steps and enzyme count, as well as simplifying the sequence space that needs to be engineered to develop an efficient biocatalyst. In this Perspective, we highlight recently reported MFBs focusing on their synthetic utility and mechanism. We also offer insight into their origin as well as comment on potential strategies for their discovery and engineering.

Smaller Differences in the Comparative Effectiveness of Biologics in Reducing Asthma-Related Hospitalizations Compared With Overall Exacerbations.

BACKGROUND: Evidence on the comparative effectiveness of respiratory biologics remains sparse. OBJECTIVE: We sought to evaluate the comparative effectiveness of omalizumab, mepolizumab, benralizumab, and dupilumab in a matched retrospective cohort of patients with asthma. METHODS: We identified patients with asthma aged ≥18 years who were incident users of these biologics between November 1, 2018, and June 30, 2023, in administrative claims data from the Food and Drug Administration's Sentinel System and Merative MarketScan Commercial Database. We compared asthma-related exacerbations and hospitalizations in the 12 months since biologic prescription in pairwise comparisons of propensity score-matched cohorts. Covariates used in matching included age, sex, allergic comorbidities, baseline asthma medications use, and the Charlson Comorbidity Index. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using negative binomial regression models. RESULTS: A total of 893 patients on mepolizumab, 1300 on benralizumab, 1170 on omalizumab, and 1863 on dupilumab were identified. The average age was 55 years, and two-thirds of the participants were female. At baseline, over 80% of these individuals had an active prescription for an inhaled corticosteroid. Almost half of patients on dupilumab had concomitant nasal polyposis compared with 6% to 13% of patients on the other biologics. Covariates were balanced after matching. In matched analyses, dupilumab was associated with the lowest incidence of exacerbations over the follow-up period (vs dupilumab): mepolizumab (IRR: 1.36; 95% CI: 1.12, 1.64), omalizumab (IRR: 1.33; 95% CI: 1.13, 1.58), benralizumab (IRR: 1.19; 95% CI: 1.00, 1.41). For exacerbations leading to hospitalizations, benralizumab and mepolizumab were associated with the lowest incidence of hospitalizations, and the greatest difference was between mepolizumab versus dupilumab (IRR: 0.76; 95% CI: 0.56, 1.03). CONCLUSIONS: Dupilumab was associated with the lowest incidence of overall exacerbations, and mepolizumab with the lowest incidence of asthma hospitalizations in this administrative claims-based cohort of individuals with asthma. Despite matching propensity scores, residual confounding, such as baseline eosinophil count, may explain some of these findings.

Evaluating palatability in young children: a mini-review of relevant physiology and assessment techniques.

The palatability of pediatric pharmaceutical products plays a crucial role of influencing medication compliance. Rejection of unpalatable medications can potentially lead to treatment failure which can have immediate and delayed consequences. With advances in both the food and pharmaceutical industries, the systematic assessment of palatability has gained importance. Various methods such as visual analogue scales, facial hedonic scales, and facial recognition software, have been employed to assess palatability. While proven to be useful, these methods have significant limitations and may not be workable for young children. Despite these advancements, a universally accepted "gold standard" for assessing pediatric mediation palatability, recognized by drug regulatory agencies, is yet to be established.

Risk Factors of Failure in 228 Periprosthetic Distal Femur Fractures: A Multicenter Study.

OBJECTIVES: To identify risk factors of reoperation to promote union or to address deep surgical-site infection (DSSI) in periprosthetic distal femur fractures treated with lateral distal femoral locking plates (LDFLPs). DESIGN: Multicenter retrospective cohort study. SETTING: Ten level-I trauma centers. PATIENT SELECTION CRITERIA: Patients with Orthopaedic Trauma Association/Association of Osteosynthesis (OTA/AO) 33A or 33C periprosthetic distal femur fractures who underwent surgical fixation between January 2012 and December 2019 exclusively using LDFLPs were eligible for inclusion. Patients with pathologic fractures or with follow-up less than 3 months without an outcome event (unplanned reoperation to promote union or for deep surgical infection) before this time point were excluded. Fracture fixation constructs used medial plates, intramedullary nails, or hybrid fixation constructs were excluded from analysis. OUTCOME MEASURES AND COMPARISONS: To examine the influence of patient demographics, injury characteristics, and features of the fracture fixation construct on the occurrence of unplanned reoperation to promote union or to address a DSSI. RESULTS: There was an 8.3% rate (19/228) of unplanned reoperation to promote union. Predictive factors for the need for reoperation to promote union included increasing body mass index (odds ratio [OR] = 1.09; 95% confidence interval [CI]: 1.02-1.16; P = 0.01), increasing number of screws in the distal fracture segment (OR = 1.73; 95% CI: 1.06-2.95; P = 0.03), and decreasing proportion of proximal segment screws that are locking (OR = 0.17; 95% CI: 0.03-0.70; P = 0.02) There was a 4.8% rate (11/228) of reoperation to address DSSI. There were no statistically significant predictive factors identified as risk factors of the need for reoperation to address DSSI ( P > 0.05). CONCLUSIONS: 8.3% of periprosthetic distal femur fractures treated at 10 centers with LDFLPs underwent unplanned reoperation to promote union. Increasing patient body mass index and increasing number of screws in the distal fracture segment were found to be predictive factors, whereas increased locking screws in the proximal segment were found to be protective. 4.8% of patients in this cohort underwent reoperation to address DSSI. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Nail Plate Combination Fixation Versus Lateral Locked Plating for Distal Femur Fractures: A Multicenter Experience.

OBJECTIVES: To (1) report on clinical, radiographic, and functional outcomes after nail-plate fixation (NPF) of distal femur fractures and (2) compare outcomes after NPF with a propensity matched cohort of fractures treated with single precontoured lateral locking plates. DESIGN: Multicenter retrospective cohort study. SETTING: Ten Level 1 trauma centers. PATIENTS/PARTICIPANTS: Patients with OTA/AO 33A or 33C fractures. INTERVENTION: Fixation with (1) retrograde intramedullary nail combined with lateral locking plate (n = 33) or (2) single precontoured lateral locking plate alone (n = 867). MAIN OUTCOME MEASUREMENTS: The main outcomes of interest were all-cause unplanned reoperation and presence of varus collapse at final follow-up. RESULTS: One nail-plate patient underwent unplanned reoperation excluding infection and 2 underwent reoperation for infection at an average of 57 weeks after surgery. No nail-plate patients required unplanned reoperation to promote union and none exhibited varus collapse. More than 90% were ambulatory with no or minimal pain at final follow-up. In comparison, 7 of the 30 matched lateral locked plating patients underwent all-cause unplanned reoperation excluding infection (23% vs. 3%, P = 0.023), and an additional 3 lateral locked plating patients were found to have varus collapse on final radiographs (10% vs. 0%, P = 0.069). CONCLUSIONS: Despite a high proportion of high-energy, open, and comminuted fractures, no NPF patients underwent unplanned reoperation to promote union or demonstrated varus collapse. Propensity score matched analysis revealed significantly lower rates of nonunion for NPF compared with lateral locked plating alone. Larger studies are needed to identify which distal femur fracture patients would most benefit from NPF. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Utilization, user characteristics, and adverse outcomes of insulin glargine originators and follow-on drug in patients with diabetes in the United States.

BACKGROUND: The first follow-on drug (Basaglar) of the originator insulin glargine (Lantus), a long-acting insulin for treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM), was approved in 2015 in the United States. Information on the uptake, user characteristics, and outcomes of follow-on insulin remains sparse. OBJECTIVE: To describe the utilization, user characteristics, and health outcomes of the follow-on insulin glargine and insulin glargine originators in a large, distributed network of primarily commercially insured patients in the United States. METHODS: We used health care claims data in the US Food and Drug Administration's Sentinel common data model format across 5 research partners in the Biologics & Biosimilars Collective Intelligence Consortium distributed research network. Sentinel analytic tools were used to identify adult users of insulin glargine between January 1, 2011, and February 28, 2021, and describe patient demographics, baseline clinical characteristics, and adverse health events among users of the originators and the follow-on drug, stratified by diabetes type. RESULTS: We identified 508,438 users of originator drugs and 63,199 users of the follow-on drug. The proportions of the follow-on drug users among total insulin glargine users were 9.1% (n = 7,070) for T1DM and 11.4% (n=56,129) for T2DM. Follow-on use rose from 8.2% in 2017 to 24.8% in 2020, accompanied by a steady decrease in the use of originator drugs. Demographics of the users of the originators and follow-on drug were similar among the T1DM and T2DM groups. Overall, follow-on users had poorer baseline health profile and higher proportions of episodes with adverse events in the follow-up. CONCLUSIONS: We found evidence of increased uptake of the follow-on drug relative to the originator products in the post-2016 period. The differences in the base-line clinical characteristics between users of the originator products and the follow-on drug and their relationship with health outcomes merit further research. DISCLOSURES: Sengwee Toh consults for Pfizer, Inc., and TriNetX, LLC. This study was funded by the BBCIC.

How honey bees make fast and accurate decisions.

Honey bee ecology demands they make both rapid and accurate assessments of which flowers are most likely to offer them nectar or pollen. To understand the mechanisms of honey bee decision-making, we examined their speed and accuracy of both flower acceptance and rejection decisions. We used a controlled flight arena that varied both the likelihood of a stimulus offering reward and punishment and the quality of evidence for stimuli. We found that the sophistication of honey bee decision-making rivalled that reported for primates. Their decisions were sensitive to both the quality and reliability of evidence. Acceptance responses had higher accuracy than rejection responses and were more sensitive to changes in available evidence and reward likelihood. Fast acceptances were more likely to be correct than slower acceptances; a phenomenon also seen in primates and indicative that the evidence threshold for a decision changes dynamically with sampling time. To investigate the minimally sufficient circuitry required for these decision-making capacities, we developed a novel model of decision-making. Our model can be mapped to known pathways in the insect brain and is neurobiologically plausible. Our model proposes a system for robust autonomous decision-making with potential application in robotics.

In the natural world, decision-making processes are often intricate and challenging. Animals frequently encounter situations where they have limited information on which to rely to guide them, yet even simple choices can have far-reaching impact on survival. Each time a bee sets out to collect nectar, for example, it must use tiny variations in colour or odour to decide which flower it should land on and explore. Each 'mistake' is costly, wasting energy and exposing the insect to potential dangers. To learn how to refine their choices through trial-and-error, bees only have at their disposal a brain the size of a sesame seed, which contains fewer than a million neurons. And yet, they excel at this task, being both quick and accurate. The underlying mechanisms which drive these remarkable decision-making capabilities remain unclear. In response, MaBouDi et al. aimed to explore which strategies honeybees adopt to forage so effectively, and the neural systems that may underlie them. To do so, they released the insects in a 'field' containing artificial flowers in five different colours. The bees were trained to link each colour with a certain likelihood of receiving either a sugary liquid (reward) or bitter quinine (punishment); they were then tested on this knowledge. Next, MaBouDi et al. recorded how the bees would navigate a 'reduced evidence' test, where the colour of the flowers were ambiguous and consisted in various blends of the originally rewarded or punished colours; and a 'reduced reward likelihood' test, where the sweet recompense was offered less often than before. Response times and accuracy rates revealed a complex pattern of decision-making processes. How quickly the insects made a choice, and the types of mistakes they made (such as deciding to explore a non-rewarded flower, or to ignore a rewarded one) were dependent on both the quality of the evidence and the certainty of the reward. Such sophistication and subtlety in decision-making is comparable to that of primates. Next, MaBouDi et al. developed a computational model which could faithfully replicate the pattern of decisions exhibited by the bees, while also being plausible biologically. This approach offered insights into how a small brain could execute such complex choices 'on the fly', and the type of neural circuits that would be required. Going forward, this knowledge could be harnessed to design more efficient decision-making algorithms for artificial systems, and in particular for autonomous robotics.

Speciation of Phosphorus in Pet Foods by Solid-State 31P-MAS-NMR Spectroscopy.

Solid-state magic angle spinning 31P NMR spectroscopy is used to identify and quantify phosphorus-containing species in pet foods. The measurement is challenging due to the long spin-lattice relaxation times (T1s). Data acquisition times are shortened by acquiring data with a tip angle smaller than 90° and shortening the repetition time. However, the spin-lattice relaxation times (T1s) of the different 31P compounds are quite different, necessitating a separate measurement for each compound in the pet food. Knowledge of T1 is used to calculate the relative amount of 31P in the samples. Samples of known concentration are also measured, enabling the quantitative measurement of total phosphorus content.

Asynchrony rescues statistically optimal group decisions from information cascades through emergent leaders.

It is usually assumed that information cascades are most likely to occur when an early but incorrect opinion spreads through the group. Here, we analyse models of confidence-sharing in groups and reveal the opposite result: simple but plausible models of naive-Bayesian decision-making exhibit information cascades when group decisions are synchronous; however, when group decisions are asynchronous, the early decisions reached by Bayesian decision-makers tend to be correct and dominate the group consensus dynamics. Thus early decisions actually rescue the group from making errors, rather than contribute to it. We explore the likely realism of our assumed decision-making rule with reference to the evolution of mechanisms for aggregating social information, and known psychological and neuroscientific mechanisms.

Identification of cancer chemotherapy regimens and patient cohorts in administrative claims: challenges, opportunities, and a proposed algorithm.

BACKGROUND: Real-world evidence is a valuable source of information in healthcare. This study describes the challenges and successes during algorithm development to identify cancer cohorts and multi-agent chemotherapy regimens from claims data to perform a comparative effectiveness analysis of granulocyte colony stimulating factor (G-CSF) use. METHODS: Using the Biologics and Biosimilars Collective Intelligence Consortium's Distributed Research Network, we iteratively developed and tested a de novo algorithm to accurately identify patients by cancer diagnosis, then extract chemotherapy and G-CSF administrations for a retrospective study of prophylactic G-CSF. RESULTS: After identifying patients with cancer and subsequent chemotherapy exposures, we observed only 12% of patients with cancer received chemotherapy, which is fewer than expected based on prior analyses. Therefore, we reversed the initial inclusion criteria to identify chemotherapy receipt, then prior cancer diagnosis, which increased the number of patients from 2,814 to 3,645, or 68% of patients receiving chemotherapy had diagnoses of interest. Additionally, we excluded patients with cancer diagnoses that differed from those of interest in the 183 days before the index date of G-CSF receipt, including early-stage cancers without G-CSF or chemotherapy exposure. By removing this criterion, we retained 77 patients who were previously excluded. Finally, we incorporated a 5-day window to identify all chemotherapy drugs administered (excluding oral prednisone and methotrexate, as these medications may be used for other non-malignant conditions) as patients may fill oral prescriptions days to weeks prior to infusion. This increased the number of patients with chemotherapy exposures of interest to 6,010. The final cohort of included patients, based on G-CSF exposure, increased from 420 from the initial algorithm to 886 using the final algorithm. CONCLUSIONS: Medications used for multiple indications, sensitivity and specificity of administrative codes, and relative timing of medication exposure must all be evaluated to identify patient cohorts receiving chemotherapy from claims data.

Predictors of Deep Infection After Distal Femur Fracture: A Multicenter Study.

OBJECTIVES: To identify potentially modifiable risk factors for deep surgical site infection after distal femur fracture. DESIGN: Multicenter retrospective cohort study. SETTING: Ten Level-I trauma centers. PATIENTS/PARTICIPANTS: Patients with OTA/AO 33A or C distal femur fractures (n = 1107). INTERVENTION: Surgical fixation of distal femur fracture. MAIN OUTCOME MEASUREMENT: The outcome of interest was deep surgical site infection. RESULTS: There was a 7% rate (79/1107) of deep surgical site infection. In the multivariate analysis, predictive factors included alcohol abuse [odds ratio (OR) = 2.36; 95% confidence interval (CI), 1.17-4.46; P = 0.01], intra-articular injury (OR = 1.73; 95% CI, 1.01-3.00; P = 0.05), vascular injury (OR = 3.90; 95% CI, 1.63-8.61; P < 0.01), the use of topical antibiotics (OR = 0.50; 95% CI, 0.25-0.92; P = 0.03), and the duration of the surgery (OR = 1.15 per hour; 95% CI, 1.01-1.30; P = 0.04). There was a nonsignificant trend toward an association between infection and type III open fracture (OR = 1.73; 95% CI, 0.94-3.13; P = 0.07) and lateral approach (OR = 1.60; 95% CI, 0.95-2.69; P = 0.07). The most frequently cultured organisms were methicillin-resistant Staphylococcus aureus (22%), methicillin-sensitive Staphylococcus aureus (20%), and Enterobacter cloacae (11%). CONCLUSIONS: Seven percent of distal femur fractures developed deep surgical site infections. Alcohol abuse, intra-articular fracture, vascular injury, and increased surgical duration were risk factors, while the use of topical antibiotics was protective. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors for Reoperation to Promote Union in 1111 Distal Femur Fractures.

OBJECTIVES: To identify modifiable and nonmodifiable risk factors for reoperation to promote union after distal femur fracture. DESIGN: Multicenter retrospective cohort study. SETTING: Ten Level-I trauma centers. PATIENTS/PARTICIPANTS: Patients with OTA/AO 33A or C distal femur fractures (n = 1111). INTERVENTION: Surgical fixation of distal femur fracture. Fixation constructs were classified as lateral plate, dual plate, nail, or nail plate combination. MAIN OUTCOME MEASUREMENTS: The outcome of interest was unplanned reoperation to promote union. RESULTS: There was an 11% (121/1111) rate of unplanned reoperation to promote union. In the multivariate analysis, predictive factors included body mass index [odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.06-1.32; P < 0.01], intra-articular fracture (OR = 1.57; 95% CI, 1.01-2.45; P = 0.04), type III open injury (OR = 2.29; 95% CI, 1.41-3.72; P < 0.01), the presence of medial comminution (OR = 1.85; 95% CI, 1.14-3.06; P = 0.01), and medial translation on postoperative radiographs (OR = 1.23 per one 10th of condylar width; 95% CI, 1.01-1.48; P = 0.03). Construct type was not significantly predictive. CONCLUSIONS: Eleven percent of distal femur fractures underwent unplanned reoperation to promote union. Body mass index, intra-articular fracture, type III open injury, medial comminution, and medial translation on postoperative radiographs were predictive factors. Construct type was not associated with unplanned reoperation; however, this conclusion was limited by small numbers in the dual plate and nail plate groups. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Using the IMEDS distributed database for epidemiological studies in type 2 diabetes mellitus.

INTRODUCTION: This study aimed to assess data relevancy and data quality of the Innovation in Medical Evidence Development and Surveillance System Distributed Database (IMEDS-DD) for diabetes research and to evaluate comparability of its type 2 diabetes cohort to the general type 2 diabetes population. RESEARCH DESIGN AND METHODS: A retrospective study was conducted using the IMEDS-DD. Eligible members were adults with a medical encounter between April 1, 2018 and March 31, 2019 (index period). Type 2 diabetes and co-existing conditions were determined using all data available from April 1, 2016 to the most recent encounter within the index period. Type 2 diabetes patient characteristics, comorbidities and hemoglobin A1c (HbA1c) values were summarized and compared with those reported in national benchmarks and literature. RESULTS: Type 2 diabetes prevalence was 12.6% in the IMEDS-DD. Of 4 14 672 patients with type 2 diabetes, 52.8% were male, and the mean age was 65.0 (SD 13.3) years. Common comorbidities included hypertension (84.5%), hyperlipidemia (82.8%), obesity (45.3%), and cardiovascular disease (44.7%). Moderate-to-severe chronic kidney disease was observed in 20.2% patients. The most commonly used antihyperglycemic agents included metformin (35.7%), sulfonylureas (14.8%), and insulin (9.9%). Less than one-half (48.9%) had an HbA1c value recorded. These findings demonstrated the notable similarity in patient characteristics between type 2 diabetes populations identified within the IMEDS-DD and other large databases. CONCLUSIONS: Despite the limitations related to HbA1c data, our findings indicate that the IMEDS-DD contains robust information on key data elements to conduct pharmacoepidemiological studies in diabetes, including member demographic and clinical characteristics and health services utilization.

Synthesis of Stereoenriched Piperidines via Chemo-Enzymatic Dearomatization of Activated Pyridines.

The development of efficient and sustainable methods for the synthesis of nitrogen heterocycles is an important goal for the chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds and their precursors. A potential biocatalytic approach to the synthesis of this privileged scaffold would be the asymmetric dearomatization of readily assembled activated pyridines. However, nature is yet to yield a suitable biocatalyst specifically for this reaction. Here, by combining chemical synthesis and biocatalysis, we present a general chemo-enzymatic approach for the asymmetric dearomatization of activated pyridines for the preparation of substituted piperidines with precise stereochemistry. The key step involves a stereoselective one-pot amine oxidase/ene imine reductase cascade to convert N-substituted tetrahydropyridines to stereo-defined 3- and 3,4-substituted piperidines. This chemo-enzymatic approach has proved useful for key transformations in the syntheses of antipsychotic drugs Preclamol and OSU-6162, as well as for the preparation of two important intermediates in synthetic routes of the ovarian cancer monotherapeutic Niraparib.

basicsynbio and the BASIC SEVA collection: software and vectors for an established DNA assembly method.

Standardized deoxyribonucleic acid (DNA) assembly methods utilizing modular components provide a powerful framework to explore designs and iterate through Design-Build-Test-Learn cycles. Biopart Assembly Standard for Idempotent Cloning (BASIC) DNA assembly uses modular parts and linkers, is highly accurate, easy to automate, free for academic and commercial use and enables hierarchical assemblies through an idempotent format. These features enable applications including pathway engineering, ribosome binding site (RBS) tuning, fusion protein engineering and multiplexed guide ribonucleic acid (RNA) expression. In this work, we present basicsynbio, open-source software encompassing a Web App (https://basicsynbio.web.app/) and Python Package (https://github.com/LondonBiofoundry/basicsynbio), enabling BASIC construct design via simple drag-and-drop operations or programmatically. With basicsynbio, users can access commonly used BASIC parts and linkers while designing new parts and assemblies with exception handling for common errors. Users can export sequence data and create instructions for manual or acoustic liquid-handling platforms. Instruction generation relies on the BasicBuild Open Standard, which is parsed for bespoke workflows and is serializable in JavaScript Object Notation for transfer and storage. We demonstrate basicsynbio, assembling 30 vectors using sequences including modules from the Standard European Vector Architecture (SEVA). The BASIC SEVA vector collection is compatible with BASIC and Golden Gate using BsaI. Vectors contain one of six antibiotic resistance markers and five origins of replication from different compatibility groups. The collection is available via Addgene under an OpenMTA agreement. Furthermore, vector sequences are available from within the basicsynbio application programming interface with other collections of parts and linkers, providing a powerful environment for designing assemblies for bioengineering applications. Graphical Abstract.

Magnitude-sensitive reaction times reveal non-linear time costs in multi-alternative decision-making.

Optimality analysis of value-based decisions in binary and multi-alternative choice settings predicts that reaction times should be sensitive only to differences in stimulus magnitudes, but not to overall absolute stimulus magnitude. Yet experimental work in the binary case has shown magnitude sensitive reaction times, and theory shows that this can be explained by switching from linear to multiplicative time costs, but also by nonlinear subjective utility. Thus disentangling explanations for observed magnitude sensitive reaction times is difficult. Here for the first time we extend the theoretical analysis of geometric time-discounting to ternary choices, and present novel experimental evidence for magnitude-sensitivity in such decisions, in both humans and slime moulds. We consider the optimal policies for all possible combinations of linear and geometric time costs, and linear and nonlinear utility; interestingly, geometric discounting emerges as the predominant explanation for magnitude sensitivity.

Three-Component Stereoselective Enzymatic Synthesis of Amino-Diols and Amino-Polyols.

Amino-polyols represent attractive chemical building blocks but can be challenging to synthesize because of the high density of asymmetric functionalities and the need for extensive protecting-group strategies. Here we present a three-component strategy for the stereoselective enzymatic synthesis of amino-diols and amino-polyols using a diverse set of prochiral aldehydes, hydroxy ketones, and amines as starting materials. We were able to combine biocatalytic aldol reactions, using variants of d-fructose-6-phosphate aldolase (FSA), with reductive aminations catalyzed by IRED-259, identified from a metagenomic library. A two-step process, without the need for intermediate isolation, was developed to avoid cross-reactivity of the carbonyl components. Stereoselective formation of the 2R,3R,4R enantiomers of amino-polyols was observed and confirmed by X-ray crystallography.

Enzymatic N-Allylation of Primary and Secondary Amines Using Renewable Cinnamic Acids Enabled by Bacterial Reductive Aminases.

Allylic amines are a versatile class of synthetic precursors of many valuable nitrogen-containing organic compounds, including pharmaceuticals. Enzymatic allylic amination methods provide a sustainable route to these compounds but are often restricted to allylic primary amines. We report a biocatalytic system for the reductive N-allylation of primary and secondary amines, using biomass-derivable cinnamic acids. The two-step one-pot system comprises an initial carboxylate reduction step catalyzed by a carboxylic acid reductase to generate the corresponding α,ß-unsaturated aldehyde in situ. This is followed by reductive amination of the aldehyde catalyzed by a bacterial reductive aminase pIR23 or BacRedAm to yield the corresponding allylic amine. We exploited pIR23, a prototype bacterial reductive aminase, self-sufficient in catalyzing formal reductive amination of α,ß-unsaturated aldehydes with various amines, generating a broad range of secondary and tertiary amines accessed in up to 94% conversion under mild reaction conditions. Analysis of products isolated from preparative reactions demonstrated that only selective hydrogenation of the C=N bond had occurred, preserving the adjacent alkene moiety. This process represents an environmentally benign and sustainable approach for the synthesis of secondary and tertiary allylic amine frameworks, using renewable allylating reagents and avoiding harsh reaction conditions. The selectivity of the system ensures that bis-allylation of the alkylamines and (over)reduction of the alkene moiety are avoided.